Effect of nikethamide (coramine) on incorporation of radioactive phosphate into rat liver deoxypentosenucleic acid.

Examples of substances reported to stimulate liver growth are few. Coramine (nikethamide, or diethylnicotinamide) causes an increase in the absolute, fat-free weight of the liver of the young rat and would appear to qualify as one of these. The effect was first noted by Coulson and Brazda in 1947 (5) in 45-50-gm. rats fed 1.0 per cent levels of Coramine in a high protein diet. It was an un expected finding and, to date, remains unex plained. A series of studies by these investigators (2-7) established that the effect was not shown by 1.0 per cent dietary levels of a-, ß, or 7-picoline, a-picolinic acid, nicotinic acid, nicotinamide, or isonicotinic acid, or by their respective methochloride derivatives, nor was it shown by monoethylnicotinamide or by the methochloride of coramine itself. These findings suggested that the action on the liver requires both the unsubstituted heterocyclic nitrogen and the diethyl substituted amide nitrogen. Pyridine and quinoline both in creased liver weight, but in these cases there was evidence of a harmful effect on the liver. Coramine increased the percentage of fat in the liver by about 30 per cent and increased the total protein in the liver (but not the percentage) by 33 per cent. The dry weight and fat-free weight of the liver, as well as the wet weight, showed sig nificant increases, and the water content a slight decrease. Tissue sections showed increased num bers of mitotic figures and binucleate cells, but no evidence of liver damage beyond the fatty change. Neither choline nor methionine was able to prevent the increase in absolute fat-free liver